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Towards application of 44 Sc for diagnostic nuclear medicine, a 44 Ti/ 44 Sc generator based on an inorganic resin has been evaluated. Unlike other radionuclide generators used for medical applications, the long-term retention of the parent 44 Ti is vital due to its long half life. Herein, tin dioxide (SnO 2 ), a robust inorganic-based resin, has been synthesized and used as the stationary phase for a 44 Ti/ 44 Sc generator. The sorption behavior of 44 Ti/ 44 Sc was tested on SnO 2 with varying acids, concentrations, and times. Preliminary batch study results showed >88 % 44 Ti retention to the resin at lower acid concentrations (0.05 M HNO 3 and 0.05 M HCl). A pilot generator was evaluated for a year, demonstrating 85.3 ± 2.8 % 44 Sc elution yields and 0.71 ± 0.14 % 44 Ti breakthrough in 5 M HNO 3 . Based on capacity studies, a 7.4 MBq (200 µCi) upscaled generator system was constructed for further evaluation of the SnO 2 resin stability and the efficacy of the eluted 44 Sc for radiolabeling. 44 Sc could be regularly eluted from this generator in 5 M HNO 3 with an overall average radiochemical yield 84.7 ± 9.5 %. Post-elution processing of the 44 Sc with DGA-normal resin removed all 44 Ti present and allowed for high 44 Sc-DOTA labeling yields of 94.2 ± 0.5 %. Overall, SnO 2 has been shown to be a viable material for a 44 Ti/ 44 Sc generator., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Melissa A. Deri has patent Alkyl-substituted hydroxamate resin for use in a generator system pending to Brookhaven National Laboratory. Vanessa A. Sanders has patent Alkyl-substituted hydroxamate resin for use in a generator system pending to Brookhaven National Laboratory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Three isotopes of scandium─ 43 Sc, 44 Sc, and 47 Sc─have attracted increasing attention as potential candidates for use in imaging and therapy, respectively, as well as for possible theranostic use as an elementally matched pair. Here, we present the octadentate chelator 3,4,3-(LI-1,2-HOPO) (or HOPO), an effective chelator for hard cations, as a potential ligand for use in radioscandium constructs with simple radiolabeling under mild conditions. HOPO forms a 1:1 Sc-HOPO complex that was fully characterized, both experimentally and theoretically. [ 47 Sc]Sc-HOPO exhibited good stability in chemical and biological challenges over 7 days. In healthy mice, [ 43,47 Sc]Sc-HOPO cleared the body rapidly with no signs of demetalation. HOPO is a strong candidate for use in radioscandium-based radiopharmaceuticals.

Several hydroxamate-based resins were synthesized and tested for use in 44 Ti/ 44 Sc generator systems in small scale experiments (740 kBq 44 Ti). The most promising resin was tested further in larger scale generator studies (37 MBq). This resin displayed impressive retention of 44 Ti over several elutions, and high quantities of 44 Sc were obtained in small volumes of dilute HCl eluents. Initial radiolabeling experiments were conducted and demonstrated the possibility of direct radiolabeling of the generator produced 44 Sc with DOTA., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Ltd.)

In recent years, there has been an increased interest in 44 Ti/ 44 Sc generators as an onsite source of 44 Sc for medical applications without needing a proximal cyclotron. The relatively short half-life (3.97 hours) and high positron branching ratio (94.3%) of 44 Sc make it a viable candidate for positron emission tomography (PET) imaging. This review discusses current 44 Ti/ 44 Sc generator designs, focusing on their chemistry, drawbacks, post-elution processing, and relevant preclinical studies of the 44 Sc for potential PET radiopharmaceuticals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The continual development of radiopharmaceutical agents for the field of nuclear medicine is integral to promoting the necessity of personalized medicine. One way to greatly expand the selection of radiopharmaceuticals available is to broaden the range of radionuclides employed in such agents. Widening the scope of development to include radiometals with their variety of physical decay characteristics and chemical properties opens up a myriad of possibilities for new actively targeted molecules and bioconjugates. This is especially true to further advance the imaging and treatment of disease in the brain. Over the past few decades, imaging of disease in the brain has heavily relied on agents which exploit metabolic uptake. However, through utilizing the broad range of physical characteristics that radiometals offer, the ability to target other processes has become more available. The varied chemistries of radiometals also allows for them to incorporated into specifically designed diverse constructs. A major limitation to efficient treatment of disease in the brain is the ability for relevant agents to penetrate the blood-brain barrier. Thus, along with efficient disease targeting, there must be intentional thought put into overcoming this challenge. Here, we review the current field of radiometal-based agents aimed at either imaging or therapy of brain disease that have been evaluated through at least in vivo studies.

Recent events in America in 2020 have stimulated a worldwide movement to dismantle anti-Black racism in all facets of our lives. Anti-Black racism is, as defined by the Movement for Black Lives, a "term used to specifically describe the unique discrimination, violence, and harm imposed on and impacting Black people specifically." In science, technology, engineering, and mathematics (STEM), we have yet to achieve the goal and responsibility to ensure that the field reflects the diversity of our lived experiences. Members of the Women in Molecular Imaging Network (WIMIN) have come together to take a stand on diversity, equity, and inclusion in the field of molecular imaging. We strongly condemn oppression in all its forms and strive to identify and dismantle barriers that lead to inequities in the molecular imaging community and STEM as a whole. In this series coined "Visions" (Antiracism and Allyship in Action), we identify and discuss specific actionable items for improving diversity and representation in molecular imaging and ensuring inclusion of all members of the community, inclusive of race, disability, ethnicity, religion, or LGBTQ+ identity. Although the issues highlighted here extend to other under-recruited and equity-seeking groups, for this first article, we are focusing on one egregious and persistent form of discrimination: anti-Black racism. In this special article, Black women residing in America present their lived experiences in the molecular imaging field and give candid insights into the challenges, frustrations, and hopes of our Black friends and colleagues. While this special article focuses on the experiences of Black women, we would like the readers to reflect on their anti-Blackness toward men, transgender, nonbinary, and gender non-conforming people. From the vulnerability we have asked of all our participants, these stories are meant to inspire and invoke active antiracist work among the readership. We present strategies for dismantling systemic racism that research centers and universities can implement in the recruitment, retention, mentorship, and development of Black trainees and professionals. We would like to specifically acknowledge the Black women who took the time to be interviewed, write perspectives, and share their lived experiences in hopes that it will inspire genuine and lasting change.

Molecular imaging is a non-invasive process that enables the visualization, characterization, and quantitation of biological processes at the molecular and cellular level. With the emergence of theragnostic agents to diagnose and treat disease for personalized medicine there is a growing need for matched pairs of isotopes. Matched pairs offer the unique opportunity to obtain patient specific information from SPECT or PET diagnostic studies to quantitate in vivo function or receptor density to inform and tailor therapeutic treatment. There are several isotopes of arsenic that have emissions suitable for either or both diagnostic imaging and radiotherapy. Their half-lives are long enough to pair them with peptides and antibodies which take longer to reach maximum uptake to facilitate improved patient pharmacokinetics and dosimetry then can be obtained with shorter lived radionuclides. Arsenic-72 even offers availability from a generator that can be shipped to remote sites and thus enhances availability. Arsenic has a long history as a diagnostic agent, but until recently has suffered from limited availability, lack of suitable chelators, and concerns about toxicity have inhibited its use in nuclear medicine. However, new production methods and novel chelators are coming online and the use of radioarsenic in the pico and nanomolar scale is well below the limits associated with toxicity. This manuscript will review the production routes, separation chemistry, radiolabeling techniques and in vitro/in vivo studies of three medically relevant isotopes of arsenic (arsenic-74, arsenic-72, and arsenic-77)., (Copyright © 2020. Published by Elsevier Inc.)

Targeted alpha therapy (TAT) is an area of research with rapidly increasing importance as the emitted alpha particle has a significant effect on inducing cytotoxic effects on tumor cells while mitigating dose to normal tissues. Two significant isotopes of interest within the area of TAT are thorium-227 and actinium-225 due to their nuclear characteristics. Both isotopes have physical half-lives suitable for coordination with larger biomolecules, and additionally actinium-225 has potential to serve as an in vivo generator. In this review, the authors will discuss the production, purification, labeling reactions, and biological studies of actinium-225 and thorium-227 complexes and clinical studies., (Copyright © 2020. Published by Elsevier Inc.)

Purpose: The increasing interest and availability of non-standard positron-emitting radionuclides has heightened the relevance of radionuclide choice in the development and optimization of new positron emission tomography (PET) imaging procedures, both in preclinical research and clinical practice. Differences in achievable resolution arising from positron range can largely influence application suitability of each radionuclide, especially in small-ring preclinical PET where system blurring factors due to annihilation photon acollinearity and detector geometry are less significant. Some resolution degradation can be mitigated with appropriate range corrections implemented during image reconstruction, the quality of which is contingent on an accurate characterization of positron range., Procedures: To address this need, we have characterized the positron range of several standard and non-standard PET radionuclides (As-72, F-18, Ga-68, Mn-52, Y-86, and Zr-89) through imaging of small-animal quality control phantoms on a benchmark preclinical PET scanner. Further, the Particle and Heavy Ion Transport code System (PHITS v3.02) code was utilized for Monte Carlo modeling of positron range-dependent blurring effects., Results: Positron range kernels for each radionuclide were derived from simulation of point sources in ICRP reference tissues. PET resolution and quantitative accuracy afforded by various radionuclides in practicable imaging scenarios were characterized using a convolution-based method based on positron annihilation distributions obtained from PHITS. Our imaging and simulation results demonstrate the degradation of small animal PET resolution, and quantitative accuracy correlates with increasing positron energy; however, for a specific "benchmark" preclinical PET scanner and reconstruction workflow, these differences were observed to be minimal given radionuclides with average positron energies below ~ 400 keV., Conclusion: Our measurements and simulations of the influence of positron range on PET resolution compare well with previous efforts documented in the literature and provide new data for several radionuclides in increasing clinical and preclinical use. The results will support current and future improvements in methods for positron range corrections in PET imaging.

A pentapeptide macrocyclic ligand, KYCAR (lysyl-tyrosyl-cystyl-alanyl-arginine), has been designed as a potential chelating ligand for SPECT imaging and therapeutic in vivo agents. This study shows the synthesis and characterization of KYCAR complexes containing nonradioactive rhenium, 99m Tc, or 188 Re. The metal complexes were also biologically evaluated to determine in vivo distribution in healthy mice. The overall goals of this project were (1) to synthesize the Tc/Re pentapeptide complexes, (2) to identify spectroscopic methods for characterization of syn versus anti rhenium peptide complexes, (3) to analyze the ex vivo stability, and (4) to assess the biological properties of the [ 99m Tc]TcO-KYCAR and [ 188 Re]ReO-KYCAR complexes in vivo. Details on these efforts are provided below., Methods: Nat Re/ 99m Tc/ 188 ReO-KYCAR complexes were synthesized, and macroscopic species were characterized via HPLC, IR, NMR, and CD. These characterization data were compared to the crystallographic data of ReO-KYC to assist in the assignment of diastereomers and to aid in the determination of the structure of the complex., Results: The radiometal complexes were synthesized with high purity (>95%). HPLC, IR, NMR and CD data on the macroscopic nat ReO-KYCAR complexes confirm the successful complexation as well as the presence of two diastereomers in syn and anticonformations. Tracer level complexes show favorable stabilities ex vivo for 2+ h., Conclusion: Macroscopic metal complexes form diastereomers with the KYCAR ligand; however, this phenomenon is not readily observed on the tracer level due to the rapid interconversion. It was determined through pK a measurements that the macroscopic nat ReO-KYCAR complex is 0 at physiological pH. The [ 99m Tc]TcO-KYCAR is stable in vitro while the [ 188 Re]ReO-KYCAR shows 50% decomposition in PBS and serum. Biologically, the tracer level complexes clear through the hepatobiliary pathway. Some decomposition of both tracers is evident by uptake in the thyroid and stomach., (Copyright © 2018 Elsevier Inc. All rights reserved.)